Post-surgical adhesions are a major healthcare problem of significant clinical and medical economic relevance. Abdominal adhesions are not only the leading cause of small bowel obstruction but also major sources of infertility and of abdominal and pelvic pain. It could be shown that post-surgical adhesions cause at least 20% of cases of infertility and about 40% of cases of chronic pelvic pain.
The great majority of adhesions in the Western world are induced by surgery. Although it is known that their incidence may be reduced by various improvements in surgical techniques and/or better instrumentation, adhesions cannot be prevented without adjuvant therapy, since every minute trauma may induce their formation.
Therefore, significant efforts have been made for providing effective means and treatment methods for reducing or preventing such adhesions connected with surgery. Many substances or constructs have been reported to have positive effects on surgical adhesions, such as collagen films, collagen gels, sodium hyaluronate/carboxymethylcellulose film and fibrin glue (see e.g. Arnold et al., Fertility and Sterility, 73 (1) (2000), 157–161).
Unfortunately, the process of adhesion and the factors influencing the criticality of such adhesions are largely still unknown. However, it is known that fibrinolysis appears to play a pivotal role in adhesiogenesis (c. Reviews of Holmdal and Holmdal et al. in Eur. J. Surg. (1997); Suppl.577:24–31 and 56–62).
The effect of the application of fibrinogen preparations or fibrin glues on anti-adhesion is highly controversial. Many earlier reports claim the possibility of prevention of the formation of postsurgical adhesions with such fibrin glues (e.g. Brands et al., Chirurg 61 (1990): 22–26; Lindenberg et al., Ann. Chir. Gynaecol. 73 (1984): 11–13; De Iaco et al., Fertility and Sterility 62 (2) (94): 400–404 and Takeuchi et al. (J. Am. Assoc. Gynecol. Laparosc. 3 (4) (1996): 575–579) or fibrinogen preparations, such as human cryoprecipitate (Toosie et al., The American Surgeon 66 (2000): 41–45; de Virgilio et al., Arch. Surg. Vol 125, October 1990, p. 1378 ff.)
However, other reports detected no significant effect of fibrin glues in preventing adhesion formation or enhancing reproductive outcome after adhesion complications during surgery (see e.g. Marana et al., Gynecol. Obstet. Invest. 41 (1996): 199–202 and Gauwerky et al., Arch. Gynecol. Obstet. 247 (1990): 161–166).
Recent research has concentrated on the development of barriers of fibrinolytic drugs and of selected agents, such as phospholipids. Comparative tests showed that resorbable barriers, such as collagen gels, collagen films and sodium hyaluronate/carboxymethylcellulose films, were effective in significantly reducing adhesion formation, whereas use of fibrin glues led to an incidence of adhesion formation similar to that in untreated control animals (see Arnold et al.; Holmdal (see supra)). These authors also demonstrated that the types of fibrinolytic inhibitors contained in all commercially available fibrin sealants significantly increased adhesion formation both to the parietal peritoneum and to the bowel compared with untreated control animals, whereas fibrinolytic activation with a recombinant tissue type plasminogen activator eliminated adhesion formation to the injured bowel and significantly reduced the number and extent of adhesions in the parietal peritoneum compared with untreated control animals.
It is therefore an object of the present invention to provide a suitable composition as well as a method for efficiently reducing or preventing post-surgical adhesions in a patient.